Quantitative single-cell proteomics as a tool to characterize cellular hierarchies.
Erwin M. Schoof,Benjamin Furtwängler,Nil Üresin,Nicolas Rapin,Simonas Savickas,Coline Gentil,Eric R. Lechman,Eric R. Lechman,Ulrich auf dem Keller,John E. Dick,John E. Dick,Bo T. Porse +11 more
TLDR
In this article, a global single-cell mass spectrometry-based proteomics approach is proposed for large-scale single cell analyses, which can provide insights into the molecular basis for cellular heterogeneity.Abstract:
Large-scale single-cell analyses are of fundamental importance in order to capture biological heterogeneity within complex cell systems, but have largely been limited to RNA-based technologies. Here we present a comprehensive benchmarked experimental and computational workflow, which establishes global single-cell mass spectrometry-based proteomics as a tool for large-scale single-cell analyses. By exploiting a primary leukemia model system, we demonstrate both through pre-enrichment of cell populations and through a non-enriched unbiased approach that our workflow enables the exploration of cellular heterogeneity within this aberrant developmental hierarchy. Our approach is capable of consistently quantifying ~1000 proteins per cell across thousands of individual cells using limited instrument time. Furthermore, we develop a computational workflow (SCeptre) that effectively normalizes the data, integrates available FACS data and facilitates downstream analysis. The approach presented here lays a foundation for implementing global single-cell proteomics studies across the world. Single-cell proteomics can provide insights into the molecular basis for cellular heterogeneity. Here, the authors develop a multiplexed single-cell proteomics and computational workflow, and show that their strategy captures the cellular hierarchies in an Acute Myeloid Leukemia culture model.read more
Citations
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Ultra‐high sensitivity mass spectrometry quantifies single‐cell proteome changes upon perturbation
TL;DR: In this paper , the authors developed a robust workflow combining miniaturized sample preparation, very low flow-rate chromatography, and a novel trapped ion mobility mass spectrometer, resulting in a more than 10-fold improved sensitivity.
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The glycosylation in SARS-CoV-2 and its receptor ACE2.
TL;DR: In this paper, the authors reviewed the detections, substrates, biological functions of the glycosylation in SARS-CoV-2 proteins as well as the human receptor ACE2.
Journal ArticleDOI
Streamlined single-cell proteomics by an integrated microfluidic chip and data-independent acquisition mass spectrometry
Sofani Tafesse Gebreyesus,Asad Ali Siyal,Reta Birhanu Kitata,Eric T Chen,Bayarmaa Enkhbayar,Takashi Angata,Kuo I. Lin,Yu-Ju Chen,Hsiung-Lin Tu +8 more
TL;DR: In this article , a chip-DIA workflow was proposed to profile the proteomes of adherent and non-adherent malignant cells, with good reproducibility and <16% missing values between runs.
Journal ArticleDOI
Streamlined single-cell proteomics by an integrated microfluidic chip and data-independent acquisition mass spectrometry
Sofani Tafesse Gebreyesus,Asad Ali Siyal,Reta Birhanu Kitata,Eric T Chen,Bayarmaa Enkhbayar,Takashi Angata,Kuo-I Lin,Yu-Ju Chen,Hsiung-Lin Tu +8 more
TL;DR: In this paper , a chip-DIA workflow was proposed to profile the proteomes of adherent and non-adherent malignant cells, with good reproducibility and <16% missing values between runs.
Journal ArticleDOI
High-throughput and high-efficiency sample preparation for single-cell proteomics using a nested nanowell chip.
Jongmin Woo,Sarah M. Williams,Lye Meng Markillie,Song Feng,Chai-Feng Tsai,Victor Aguilera-Vazquez,Ryan L. Sontag,Ronald J. Moore,Dehong Hu,Hardeep S. Mehta,Joshua Cantlon-Bruce,Tao Liu,Joshua N. Adkins,Richard D. Smith,Geremy Clair,Ljiljana Paša-Tolić,Ying Zhu +16 more
TL;DR: In this paper, a nested nanoPOTS (N2) chip is proposed to improve protein recovery, operation robustness, and processing throughput for isobaric-labeling-based scProteomics workflow.
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Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
Dominique Bonnet,John E. Dick +1 more
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Posted Content
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction
Leland McInnes,John Healy +1 more
TL;DR: The UMAP algorithm is competitive with t-SNE for visualization quality, and arguably preserves more of the global structure with superior run time performance.